The analgesic properties of cannabis have been noted for centuries. However, the use of cannabis to treat pain is limited due to its psychoactive properties and abuse liability. Therapeutic applications may still be possible through the selective activation of peripheral cannabinoid receptors. Cannabinoid 1 (CB1) receptors have been localized to primary afferent neurons and cutaneous nerve terminals. Also, previous studies using animal models of both acute and persistent pain, such as inflammation, have demonstrated that locally administered cannabinoid receptor agonists produce peripherally mediated antihyperalgesia. The extent to which cannabinoids alter responses of nociceptors in this peripherally mediated antihyperalgesia is not currently known. [unreadable] [unreadable] Using correlative behavioral and in vivo teased-fiber electrophysiological methods, the overall objective of this proposal is to determine the peripheral neural mechanisms by which cannabinoid decrease hyperalgesia. We hypothesize that during adjuvant-evoked inflammation, activation of peripheral CB1 receptors will decrease the evoked responses of cutaneous A6 and C nociceptors and attenuate hyperalgesia. [unreadable] [unreadable] PUBLIC HEALTH RELEVANCE: [unreadable] These studies will provide insight into the peripheral mechanisms of cannabinoid-mediated analgesia. Results may have a direct impact on the future development of novel, peripherally acting medications to treat pain. [unreadable] [unreadable] [unreadable]